Data monitoring committees

A Data Monitoring Committee (DMC) — sometimes called a Data and Safety Monitoring Board (DSMB) — is an independent group of experts who monitor patient safety and treatment efficacy data while a clinical trial is ongoing.

Need for a DMC

Many randomized clinical trials are double blind, i.e. no one involved with the trial knows what treatment was given to the trial participant. This includes the participant, their doctor, and even the study personnel at the company that is sponsoring the trial. There are many extremely good reasons to conduct a trial in this manner and only after the trial database is finalized is the blind broken and the true treatment assignments disclosed.

However, these trials may go for years and there is justifiably concern about enrolling participants and exposing them to an unproven treatment without someone overseeing results. The company sponsoring the trial is blinded, so they can't perform this service. Even if they had some people who were unblinded to the results, they would be in an awkward position between concern for their corporate interests and concern for the trial participants.

The DMC is a group (typically 3 to 7 members) who are independent of the company sponsoring the trial. At least one DMC member will be a statistician. Clinicians knowledgeable about the disease indication should be represented, as well as clinicians knowledgeable in the fields of any major suspected safety effects (e.g. nephrology, cardiology). A few long, visible trials may include an ethicist or even a representative from a patient advocacy group. The DMC will convene at predetermined intervals (three to six months typically) and review unblinded results, i.e. results split by experimental and control arms. The DMC has the power to recommend termination of the study based on the evaluation of these results. There are typically three reasons a DMC might recommend termination of the study: safety concerns, outstanding benefit, and futility.

Safety concerns

The primary mandate of the DMC is to protect patient safety. If adverse events of a particularly serious type are more common in the experimental arm compared to the control arm, then the DMC would have to strongly consider termination of the study. This evaluation has to be made in consideration of risk/benefit. In many cases, the experimental arm could cause serious adverse events (chemotherapy, for example), but the resulting improvement in survival outweighs these adverse events.

Overwhelming benefit

In the rare, but fortunate, situation that the experimental arm is shown to be undeniably superior to the control arm the DMC may recommend termination of the trial. This would allow the company sponsoring the trial to get regulatory approval earlier and to allow the superior treatment to get to the patient population earlier. There are cautions here though. The statistical proof needs to be very high indeed. Also, there might be other reasons to continue, such as collecting more long-term safety data.

Futility

Futility is not as widely recognized as safety and benefit, but actually can be the most common reason to stop a trial. As an example, suppose a trial is one-half completed, but the experimental arm and the control arm have nearly identical results. It's likely in no one's interest to have this trial continue. It is extremely unlikely that the trial, should it continue to its normal end, would have the statistical proof needed to convince a regulatory agency to approve the treatment. The company sponsoring the study could save money for other projects by abandoning this trial. Also, current and potential trial participants could be freed to take other treatments, rather than this experimental treatment which is unlikely to benefit them.

References

• Susan Ellenberg, Thomas Fleming, David DeMets, Data Monitoring Committees in Clinical Trials: A Practical Perspective (John Wiley & Sons Inc., 2002) ISBN 0-471-48986-7

• David DeMets, Curt Furberg, Lawrence Friedman, Data Monitoring in Clinical Trials: A Case Studies Approach (Springer, 2006) ISBN 0-387-20330-3

• David Kerr, Lynn Shemanski, Ruth McBride (2004). "Data Monitoring Committees in Practice: Tips on using DMCs to improve trial efficiency and safety". Applied Clinical Trials. http://appliedclinicaltrialsonline.findpharma.com/appliedclinicaltrials/article/articleDetail.jsp?id=87247. 

See also

• Clinical monitoring
• Clinical trial protocol
• Institutional Review Board
• Drug development
• Pharmacovigilance
• EudraVigilance

External links

• "Guidance for Clinical Trial Sponsors: Establishment and Operation of Clinical Trial Data Monitoring Committees" (PDF). Food and Drug Administration. March 2006. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm127073.pdf. Retrieved 2009-07-12.